DYT1 Gene Mutation Research Articles

DBS treatment in an 18-year-old with refractory dystonia due to DYT1 mutation: a case report

Introduction: The term dystonia may be defined by abnormal involuntary movements or postures due to sustained or intermittent muscle contractions. One of the most common aetiologies of isolated dystonia is due to the mutation in DYT1 gene, resulting in a disorder of abnormal regulation of gene transcription and neuronal circuit development. Of all the patients with this mutation, about 30-40% will develop symptoms of the disease. Typically, the clinical manifestation of this type of dystonia will begin from the first to third decade of life, with generalized distribution, and involving more likely the lower limbs or, less frequently, the upper limbs and trunk. Objective: To present a case of an infrequent refractory dystonia due to DYT1 gene mutation in an 18-year-old male patient that was later treated with Deep Brain Stimulation (DBS). Case report: Here we report about the case of a 18-year-old male patient affected by torsion dystonia of the neck and a segment of the upper limbs. He first exhibited symptoms when he was 15 years old and, since then, has had a series of complications, such as severe pain and recurrent pneumonia. Genetic analysis identified a DYT1 gene superexpression mutation. Previous therapies had included physiotherapy, botulinum toxin injections, drugs such as primidone and clonazepam, but all with little improvement. Due to the patient's severe torsion dystonia on his right side, it was decided to implant a DBS only in the left internal globus pallidus (GPi) posteromedial area, in a brain surgery with general anesthesia that took place in March 2018. After 10 months, the same procedure was made in the right GPi, at the subthalamic nucleus, aiming to treat his dystonic tremors located in the left part of the body. The electrodes inserted were Medtronic® 3389 and the generator was Activa RC rechargeable, with 0.5 mm spacing. The following programming was set: current of 3 mA, frequency of 130 Hz and pulse width of 90 μs. The battery of the electrode was inserted in the right side of the chest due to the patient's more severe torsion. The post-operative (PO) was successful, without any deficit, being discharged from the hospital at the PO day 4 in the first surgery and day 2 and in the second. After a 2-year follow-up period, the patient presents a normal life compared to the average of his age, without any of the symptoms or complications he had before. He regularly attends physiotherapy and fitness centres to maintain muscle training.

S2208 Primary Squamous Cell Carcinoma as a Long-Term Complication of Percutaneous Endoscopic Gastrostomy Placement

Introduction: Common complications associated with percutaneous endoscopic gastrostomy (PEG) placement include aspiration, bleeding, leakage, irritation, abdominal pain, and infection. Previous case reports have described the PEG site as a location for metastatic malignancy, especially in the setting of head and neck cancers (often an indication for PEG placement). We present a rare case of primary squamous cell carcinoma (SCC) which developed in the setting of long-term PEG placement. Case Description/Methods: Patient is a 51-year-old woman with developmental delay and dystonia secondary to DYT1 gene mutation. Given her developmental delay, a PEG was placed for nutritional support and had been in place for thirty-two years. She presented with a 2-cm abscess at her PEG site and was discharged with oral antibiotics following incision and drainage (I+D). She noted persistent leakage of bloody and foul-smelling drainage from her PEG tube (figure 1). She returned with worsening irritation surrounding the PEG site and was noted to have a 5x7 cm area of erythema with overlying fluctuant abscess. Again, she underwent I+D and was started on IV antibiotics. Cross sectional imaging demonstrated irregular soft tissue thickening involving the greater curvature of the stomach, adjacent to the PEG site, extending into the gastrostomy tube tract. A biopsy of the skin surrounding the PEG tube was performed and demonstrated well-differentiated and invasive SCC. A subsequent PET scan showed locally invasive disease with PEG site involvement extending into the abdominal wall. There were no additional areas concerning for malignancy (no indications of an alternative primary site). Given the burden of locally invasive disease, surgical resection was deferred and she was offered palliative radiation. Discussion: The development of SCC at the PEG site is an uncommon occurrence and previous case reports typically describe these events as metastasis from a head/neck primary site. There has been at least one additional documented case of primary SCC at the PEG site but this occurred in an immunosuppressed patient. Chronic irritation of the skin, which is a known complication of PEG placement, possibly contributed to the development of SCC in this patient. Aggressive wound care and close monitoring for suspicious mucosal changes should be considered in patients with long-term PEG placement.Figure 1.: Squamous Cell Carcinoma along the PEG site.

Auditory-Perceptual Evaluation of Deep Brain Stimulation on Voice and Speech in Patients With Dystonia

To determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on speech and voice quality of patients with primary, medically refractory dystonia. Voices of 14 patients aged ≥18 years (males = 7 and females = 7) with primary dystonia (DYT1 gene mutation dystonia = 4, cervical dystonia = 6, and generalized dystonia = 4) with bilateral GPi DBS were assessed. Five blinded raters (two fellowship-trained laryngologists and three speech/language pathologists) evaluated audio recordings of each patient pre- and post-DBS. Perceptual voice quality was rated using the Grade, Roughness, Breathiness, Asthenia, and Strain scale and changes in speech intelligibility were assessed with the Clinical Global Impression scale of Severity instrument. Inter-rater and intrarater reliability rates for perceptual voice ratings were assessed using the kappa coefficient. Voice quality parameters showed mean improvements in Grade (P < 0.0001), Roughness (P = 0.0043), and Strain (P < 0.0001) 12 months post-DBS. Asthenia increased from baseline to 6 months (P = 0.0022) and declined significantly from 6 to 12 months (P = 0.0170). Breathiness did not change significantly over time. Speech intelligibility also improved from 6 to 12 months (P = 0.0202) and from pre-DBS to 12 months post-DBS (P = 0.0022). Grade and Strain ratings had nearly perfect and substantial inter-rater agreement (0.84 and 0.71, respectively). Voice and speech intelligibility improved after bilateral GPi DBS for dystonia. GPi DBS may emerge as a potential treatment option for patients with medically refractory laryngeal dystonia.

Abnormal blink reflex recovery cycle in manifesting and nonmanifesting carriers of the DYT1 gene mutation.

The aim of this study is to evaluate the brainstem function in DYT1 carriers manifesting clinical dystonia (MDYT1) and those without clinical symptoms (NMDYT1). Motor cortical inhibition and plasticity were found to be abnormal in MDYT1, whereas these were less abnormal in NMDYT1. However, the spinal reciprocal inhibition was abnormal in MDYT1, but normal in NMDYT1. Moreover, protein accumulation and perinuclear inclusion bodies were found in the brainstem, but not in other brain areas, in DYT1 patients. Therefore, we designed this study to investigate the brainstem physiology using the blink reflex (BR) recovery cycle test in MDYT1 and NMDYT1. We recruited eight MDYT1, five NMDYT1, and nine age-matched healthy controls. The BR recovery cycle was assessed with paired stimuli that induced the BR in a random order at interstimulus intervals of 250, 500, and 1000 ms. A two-way analysis of variance showed a significant difference between MDYT1, NMDYT1, and the healthy control (P=0.004). Post-hoc analysis showed that this was because of a significantly lower inhibition of R2 in MDYT1 and NMDYT1 compared with the controls (two-way analysis of variance: P=0.003 and 0.021, respectively). There was no difference between MDYT1 and NMDYT1 (P=0.224). The tested brainstem circuits were equally involved in MDYT1 and NMDYT1. The finding is in agreement with the pathological findings in DYT1 carriers. Together with previous findings in the motor cortex and the spinal cord, the brainstem may lie closer to the pathogenesis of dystonia than the motor cortex in DYT1 gene carriers.

INTERFAMILIAL POLYMORPHISM OF TYPE 1 DYSTONIA

Актуальность. Наиболее частой мутацией в гене TOR1A (DYT1) (9q34), обусловливающей дистонию 1-го типа (дофа-независимую форму торсионной дистонии), является делеция c.907 -909delGAG в 5-м экзоне гена (303delGlu). В российской популяции у больных цервикальной дистонией этой мутации не обнаружено.

Motor sequence learning and motor adaptation in primary cervical dystonia

Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect “contamination” rather than being directly pathological.

The functional neuroimaging correlates of psychogenic versus organic dystonia

The neurobiological basis of psychogenic movement disorders remains poorly understood and the management of these conditions difficult. Functional neuroimaging studies have provided some insight into the pathophysiology of disorders implicating particularly the prefrontal cortex, but there are no studies on psychogenic dystonia, and comparisons with findings in organic counterparts are rare. To understand the pathophysiology of these disorders better, we compared the similarities and differences in functional neuroimaging of patients with psychogenic dystonia and genetically determined dystonia, and tested hypotheses on the role of the prefrontal cortex in functional neurological disorders. Patients with psychogenic (n = 6) or organic (n = 5, DYT1 gene mutation positive) dystonia of the right leg, and matched healthy control subjects (n = 6) underwent positron emission tomography of regional cerebral blood flow. Participants were studied during rest, during fixed posturing of the right leg and during paced ankle movements. Continuous surface electromyography and footplate manometry monitored task performance. Averaging regional cerebral blood flow across all tasks, the organic dystonia group showed abnormal increases in the primary motor cortex and thalamus compared with controls, with decreases in the cerebellum. In contrast, the psychogenic dystonia group showed the opposite pattern, with abnormally increased blood flow in the cerebellum and basal ganglia, with decreases in the primary motor cortex. Comparing organic dystonia with psychogenic dystonia revealed significantly greater regional blood flow in the primary motor cortex, whereas psychogenic dystonia was associated with significantly greater blood flow in the cerebellum and basal ganglia (all P < 0.05, family-wise whole-brain corrected). Group × task interactions were also examined. During movement, compared with rest, there was abnormal activation in the right dorsolateral prefrontal cortex that was common to both organic and psychogenic dystonia groups (compared with control subjects, P < 0.05, family-wise small-volume correction). These data show a cortical–subcortical differentiation between organic and psychogenic dystonia in terms of regional blood flow, both at rest and during active motor tasks. The pathological prefrontal cortical activation was confirmed in, but was not specific to, psychogenic dystonia. This suggests that psychogenic and organic dystonia have different cortical and subcortical pathophysiology, while a derangement in mechanisms of motor attention may be a feature of both conditions.

Early registration of diffusion tensor images for group tractography of dystonia patients

To make a group comparison of diffusion tensor imaging (DTI) results of dystonia patients and controls to reveal occult pathology. We propose using an early registration method that produces sharper group images and enables us to do group tractography. Twelve dystonia patients manifesting the disease, seven nonmanifesting dystonia mutation carriers (DYT1 and DYT6 gene mutations), and eight age-matched normal control subjects were imaged for a previous study. Early and late registration methods for DTI were compared. An early registration technique for a super set was proposed, in which the diffusion-weighted images were registered to a template, gradient vectors were reoriented for each subject, and they were combined into a super set before tensor calculation. The super set included images from all subjects and was useful for group comparisons. We used results obtained from the early registration of a super set for group analysis of tracts using the deterministic fiber-tracking technique. In dystonia mutation carriers, we detected fewer fibers in the cerebello-thalamo-cortical pathways. This result agrees well with the findings of a previous study that utilized a probabilistic tractography method and demonstrated that gene carriers have less fiber tracts in the disease-involved pathway. This analysis visualized group level white matter fractional anisotropy and tract differences between dystonia patients and controls, and can be useful in understanding the pathophysiology of other nonfocal white matter diseases.

Cholinergic Dysfunction Alters Synaptic Integration between Thalamostriatal and Corticostriatal Inputs in DYT1 Dystonia

Projections from thalamic intralaminar nuclei convey sensory signals to striatal cholinergic interneurons. These neurons respond with a pause in their pacemaking activity, enabling synaptic integration with cortical inputs to medium spiny neurons (MSNs), thus playing a crucial role in motor function. In mice with the DYT1 dystonia mutation, stimulation of thalamostriatal axons, mimicking a response to salient events, evoked a shortened pause and triggered an abnormal spiking activity in interneurons. This altered pattern caused a significant rearrangement of the temporal sequence of synaptic activity mediated by M(1) and M(2) muscarinic receptors in MSNs, consisting of an increase in postsynaptic currents and a decrease of presynaptic inhibition, respectively. Consistent with a major role of acetylcholine, either lowering cholinergic tone or antagonizing postsynaptic M(1) muscarinic receptors normalized synaptic activity. Our data demonstrate an abnormal time window for synaptic integration between thalamostriatal and corticostriatal inputs, which might alter the action selection process, thereby predisposing DYT1 gene mutation carriers to develop dystonic movements.

Staged implantation of multiple electrodes in the internal globus pallidus in the treatment of primary generalized dystonia

Deep brain stimulation (DBS) is used for treating various types of dystonia. Multiple electrodes could be proposed to improve the therapeutic outcome enabling the targeting of specific neuronal populations not reached by the electrical field generated by the initially implanted electrode. The authors address the question of the feasibility and safety of staged multiple lead implantations in the sensorimotor internal globus pallidus (GPi) in primary generalized dystonia (PGD). Criteria for patient selection, surgical technique, target selection, electrical settings management, and clinical outcome are presented. Sixteen patients (8 harbored the DYT1 gene mutation) presented with PGD and were enrolled in this study. Patients underwent clinical assessment using the Burke-Fahn-Marsden Dystonia Rating Scale preoperatively and during follow-up with DBS. Prior to the addition of electrodes, the authors confirmed, by turning off stimulation, that the patient was still benefiting from DBS and that DBS settings adjustment did not provide further improvement. The second target was defined according to the position of the first electrode, to the residual volume within the sensorimotor GPi, and according to residual symptoms. The second surgery followed the same protocol as the first and the new electrode were inserted using the same bur hole as the first electrode. The addition of a new pair of electrodes was followed by significant improvement in the whole population (p = 0.005), as well as in the DYT1-negative subgroup (p = 0.012) but not in the DYT1 subgroup (p = not significant). Nevertheless, some patients did not exhibit significant additional benefit. Seven hardware-related complications occurred during the entire follow-up, 3 prior to it, and 4 after the addition of the second pair of electrodes. The addition of a second pair of electrodes in the GPi in patients with PGD with suboptimal or decaying benefit following the first surgery seems to be a safe procedure and is not followed by an increase in surgery-related complications. This staged procedure may provide further clinical improvement in patients with PGD in whom DBS effect is initially incomplete or when disease progression occurs over time. The position of the additional electrode within the GPi is determined by the available volume within the posteroventral GPi and by the distribution of the dystonic symptoms that need to be controlled.

Clinical feature and DYT1 mutation screening in primary dystonia patients from South‐West China

Clinical presentation and DYT1 status amongst Chinese patients with primary dystonia have not been well studied. One hundred and twenty patients with primary dystonia from South-West China were studied in a prospective survey for 3.5 years. Severity and the resulting disability were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). Health related quality of life (HRQL) was measured through the 36-item short-form (SF-36). The Hospital Anxiety and Depression Scale (HADS) was utilized to identify and quantify depression and anxiety. Mutations in the DYT1 exon 5 were screened by direct sequencing. Cervical dystonia was found to be the most frequent form of focal dystonia and was discovered to occur at an early age. Pain and tremor were the common associated symptoms. Family history was positive in 19.5% of the cases, with a trend of earlier onset. Depression (14.5%) and anxiety (6.6%) were the main HRQL impairments. Multiple linear regression analysis suggested that gender, depression, anxiety and functional disability were amongst the principal determinants of lower HRQL. Only one instance of DYT1 GAG deletion (1.4%) was detected in 71 patients. Our data on a cohort of Chinese patients show some difference from descriptions in other ethnic groups. This includes an earlier age of onset, a lower incidence of depression and female serving as a predictor factor of a HRQL. Similar to other cohorts, DYT1 gene mutations are rare.

Genotype–phenotype interactions in primary dystonias revealed by differential changes in brain structure

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia.This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles.By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilaterally. The explanation for this effect differs according to both gene and dystonia status: non-DYT1 adult-onset dystonia patients and asymptomatic DYT1 carriers have significantly larger basal ganglia compared to healthy subjects and symptomatic DYT1 mutation carriers. There is a significant negative correlation between severity of dystonia and basal ganglia size in DYT1 mutation carriers.We propose that differential pathophysiological and compensatory mechanisms lead to brain structure changes in non-DYT1 primary adult-onset dystonias and DYT1 gene carriers. Given the range of age of onset, there may be differential genetic modulation of brain development that in turn determines clinical expression. Alternatively, a DYT1 gene dependent primary defect of motor circuit development may lead to stress-induced remodelling of the basal ganglia and hence dystonia.

DYT1 mutations in early onset primary torsion dystonia and Parkinson disease patients in Chinese populations

Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. Moreover, dystonia and Parkinson disease share the common feature of reduced dopamine neurotransmission in the striatum, so we assumed that mutations in the DYT1 gene might have the same role in cases of early onset primary torsion dystonia (EOPTD) and early onset Parkinson disease (EOPD) that present dystonia. In this present study, 17 patients with EOPTD, 221 patients with EOPD and 164 control subjects were screened for mutations of the DYT1 gene by denaturing high performance liquid chromatography (DHPLC), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. Our results showed that the GAG deletion was identified in 7 EOPTD patients, which results in Glu302del of DYT1 gene. No mutations were found in EOPD patients and control subjects. By carefully reviewing the available literature on studies of sporadic, non-Ashkenazi Jewish populations, the results showed that the prevalence rate of DYT1 mutation was not significantly different (p=0.267) between European (27.3%) and Asian (22.2%) patients with early onset primary torsion dystonia.

Clinical and genetic characterization of a large Dutch family with primary focal dystonia

We describe a large family with a primary focal dystonia from a small Dutch village on a former island. Twenty-four individuals spanning three generations were examined by two movement-disorder neurologists. Two other movement-disorder neurologists evaluated the videos independently. Subjects were classified as "affected," "possibly affected," or "not affected." A diagnosis was defined if all the neurologists agreed on the definition. Eight definitely affected and four possibly affected subjects were detected. Clinical presentation consisted of mild cranio-cervical-brachial dystonia. Mean age at onset was 45.5 years (range, 39-56). Mean BFMDRS motor score was 4.4 (range, 1-8). Mean TWSTRS score (part I) was 11.3 (range, 8-23). Mutations in DYT1 gene and in the epsilon-sarcoglycan (SGCE) genes were not detected. We could not find linkage to the dominant DYT6, DYT7, DYT13, or the recessive DYT16 loci. The identification and accurate clinical evaluation of large dystonia families not linked to known genes is crucial for further advancement in molecular genetic characterization of focal dystonia.

Impaired body movement representation in DYT1 mutation carriers

ObjectiveThe only known genetic cause of early-onset primary torsion dystonia is the GAG deletion in the DYT1 gene. Due to the reduced penetrance, many mutation carriers remain clinically asymptomatic, despite the presence of subclinical abnormalities, mainly in the motor control circuitry. Our aim was to investigate whether the DYT1 mutation impairs the inner simulation of movements, a fundamental function for motor planning and execution, which relies upon cortical and subcortical systems, dysfunctional in dystonia. MethodsDYT1 manifesting patients, DYT1 non-manifesting carriers and control subjects were asked to fixate body (hand, foot, face) or non-body (car) stimuli on a computer screen. Stimuli were presented at different degrees of orientations and subjects had to mentally rotate them, in order to give a laterality judgement. Reaction times and accuracy were collected. ResultsDYT1 carriers, manifesting and non-manifesting dystonic symptoms, were slower in mentally rotating body parts (but not cars) than control subjects. ConclusionsThe DYT1 gene mutation is associated with a slowness in mental simulation of movements, independently from the presence of motor symptoms. SignificanceThese findings suggest that the cognitive representation of body movements may be altered subclinically in dystonia, thus contributing to the endophenotypic trait of disease.

Pallidal surgery for the treatment of primary generalized dystonia: Long-term follow-up

Objective To describe the results and long-term follow-up after functional surgery of the internal segment of the globus pallidus (GPi) in 10 patients with primary generalized dystonia. Patients and methods Nine of the 10 patients were positive for the DYT1 gene mutation. Bilateral deep brain stimulation (DBS) of the GPi was performed in three cases, bilateral pallidotomy in two, and combined surgery (unilateral GPi lesion with contralateral stimulation) in the remaining five. All patients were evaluated with the Burke–Fahn–Marsden dystonia scale (BFMDS) before, immediately after surgery, at 3 weeks, 3 and 6 months and then yearly. Follow up time ranged from 15 to 105 months (mean: 66.1 months) with six patients having more than 6 years follow up. Results All patients improved after surgery. All patients with unilateral or bilateral DBS experienced an immediate improvement before starting stimulation. The magnitude of this initial micro lesion effect did not predict the magnitude of the long-term benefit of DBS. The mean decrease in the in the BFMDS was 34%, 55%, and 65% in the movement scale; and 32%, 48%, and 49% in the disability scale for patients with bilateral pallidal DBS, combined unilateral DBS and contralateral pallidotomy, and bilateral pallidotomy, respectively. Worsening of dystonia after a plateau of sustained benefit was observed in three patients. Two patients required multiple pallidal surgeries. Adverse events included: permanent anarthria (1), misplacement of the electrode requiring further surgery (2), scalp infection (1), and hardware related problems (3). Conclusions This long-term follow up study confirms the beneficial effect of pallidal DBS or pallidotomy in primary generalized dystonia. In addition, our results extent previous observations by showing that, in these patients, (1) the microlesion effect of DBS is not predictive of long-term benefit; (2) combined DBS with contralateral pallidotomy appears to be more effective than bilateral pallidal DBS; and (3) dystonia can reappear after an initial good response during long term follow up.

Sixty hertz pallidal deep brain stimulation for primary torsion dystonia

To evaluate the safety and efficacy of 60 Hz deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 15 consecutive patients with primary dystonia. We conducted a retrospective analysis of clinic charts relative to 15 consecutive patients with medically refractory primary dystonia who underwent stereotactic implantation of DBS leads within the GPi. Twelve had the DYT1 gene mutation. Frame-based MRI and intraoperative microelectrode recording were employed for targeting. All patients were treated exclusively with stimulation at 60 Hz from therapy outset. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) served as the primary measure of symptom severity at baseline and 1, 3, 6, and 12 months after treatment. All patients tolerated DBS treatment well and showed a progressive median improvement of their BFMDRS motor subscores from 38% at 1 month to 89% at 1 year (p < 0.001, Wilcoxon rank sum test). The disability subscores were similarly improved. The clinical response to DBS allowed seven patients to completely discontinue their medications; six additional patients had reduced their medications by at least 50%. Surgical complications were limited to two superficial infections, which were treated successfully. Stimulation of the internal globus pallidus at 60 Hz is safe and effective for treating medically refractory primary dystonia.

Deep brain stimulation for torsion dystonia in children

Deep brain stimulation (DBS) at the internal globus pallidus (GPi) is an effective treatment for some patients with medically refractory torsion dystonia. In this article, we review the results of pallidal DBS surgery in children with dystonia. Details of the DBS procedure and programming of the DBS devices are discussed. Pallidal DBS is most effective in patients with primary generalized dystonia. Children and adolescents possessing the DYT1 gene mutation may respond best of all. The presence of static dystonic postures and/or fixed orthopedic contractures may limit the functional response to DBS and may require additional surgery. As a group, patients with secondary dystonias respond less well to DBS than patients with primary dystonia. However, patients with dystonia secondary to anoxic brain injury who have grossly intact basal ganglia anatomy may represent a subpopulation for whom pallidal DBS is a viable option.

Impact of bilateral pallidal stimulation on DYT1‐generalized dystonia in Japanese patients

Early-onset generalized dystonia attributable to a DYT1 gene mutation is a hyperkinetic movement disorder that responds poorly to pharmacotherapy. In this video brief, we show that continuous bilateral stimulation of the globus pallidus internus produced sustained and marked improvements in the motor symptoms and functional disabilities of Japanese patients with DYT1-generalized dystonia.

Stiff child syndrome with mutation of DYT1 gene

The authors report a Chinese boy with a DYT1 gene mutation having muscle stiffness, severe painful muscle spasm, myoclonus, and dystonia compatible with stiff child syndrome. Autoantibodies to glutamic acid decarboxylase (anti-GAD) were absent. His asymptomatic mother had a DYT1 mutation. His asymptomatic sister has diabetes mellitus and antibodies to glutamic acid decarboxylase but no DYT1 mutation.